Does hydroxyzine (an antihistamine) worsen REM (Rapid Eye Movement) behavior disorder?

Hydroxyzine and REM Sleep Behavior Disorder

Hydroxyzine should be avoided in patients with REM sleep behavior disorder (RBD) as it may potentially worsen symptoms through its anticholinergic and sedating properties.

Mechanism and Concerns

Hydroxyzine, a first-generation antihistamine, poses several concerns for patients with RBD:

• First-generation antihistamines like hydroxyzine have significant anticholinergic properties that can disrupt normal sleep architecture 1
• Hydroxyzine causes sedation that may mask RBD symptoms without addressing the underlying pathophysiology 2
• Sedating medications can increase the risk of falls and confusion in patients with RBD, particularly concerning as many RBD patients are elderly or have neurodegenerative conditions 2

Evidence from Guidelines

The American Academy of Sleep Medicine's guidelines for RBD management do not recommend hydroxyzine for RBD treatment. Instead, they recommend:

1. First-line treatments for RBD:

   • Clonazepam (0.25-2.0 mg at bedtime) 2
   • Immediate-release melatonin (3-15 mg at bedtime) 2

2. Second-line options:

   • Rivastigmine (particularly for patients with cognitive impairment) 2
   • Pramipexole (especially when periodic limb movements are present) 2

Safety Concerns with Hydroxyzine in RBD

Several specific concerns make hydroxyzine problematic for RBD patients:

• Cognitive impairment risk: Many RBD patients have or are at risk for neurodegenerative disorders, and hydroxyzine can worsen cognitive function 2, 1
• Fall risk: Hydroxyzine increases fall risk through sedation and impaired coordination, particularly dangerous in elderly RBD patients 1
• Masking symptoms: Sedation may suppress RBD behaviors without addressing the underlying pathophysiology 2
• Tolerance development: Patients can develop tolerance to hydroxyzine's sedating effects while anticholinergic side effects persist 2

Special Considerations for Different RBD Types

Isolated RBD

For isolated RBD, the American Academy of Sleep Medicine recommends:

• Clonazepam (starting at 0.25-0.5 mg) 2
• Immediate-release melatonin (starting at 3 mg, increasing by 3 mg increments to 15 mg) 2

Secondary RBD (associated with neurodegenerative disorders)

• Lower doses of clonazepam (starting at 0.25 mg) due to increased sensitivity 2
• Melatonin may be preferred due to its more favorable side effect profile 2, 3
• Rivastigmine may be appropriate for patients with cognitive impairment 2

Drug-Induced/Exacerbated RBD

• Primary approach should be discontinuation of the offending agent if safe to do so 2
• Serotonergic medications are common culprits; hydroxyzine would not address this underlying cause 2

Alternative Approaches for Sleep Disturbances in RBD Patients

If sleep disturbance is a concern in RBD patients:

• Optimize treatment of the underlying RBD with clonazepam or melatonin 2
• Address sleep hygiene and environmental safety measures 2
• Consider cognitive behavioral therapy for insomnia if comorbid insomnia exists
• For patients with anxiety, consider buspirone or SSRIs with careful monitoring for RBD exacerbation 1

Conclusion

Hydroxyzine should be avoided in patients with REM sleep behavior disorder due to its potential to worsen symptoms, increase fall risk, and cause cognitive impairment. Clonazepam and melatonin remain the first-line treatments for RBD based on current guidelines and evidence.